Lipophilic 1,3-xylyl-21-crown-6 macrocyclic polyether 2-carboxylic acids as biological mimics of the ionophore antibiotics.
Twelve lipophilic 1,3-xylyl-21-crown-6 macrocyclic polyether 2-carboxylic acids, two lariat ether 1,3-xylyl-21-crown-6 macrocyclic polyether 2-carboxylic acids, and two 1,3-xylyl-28-crown-8 macrocyclic polyether 2-carboxylic acids were synthesized and tested for in vitro antibacterial activity, in vitro stimulation of rumen propionic acid production, and in vivo anticoccidial activity in chickens. These are biological screens relevant to animal health areas where the ionophore antibiotics such as monensin have found application. While the parent structure 1 without lipophilic substituents was biologically inactive, the lipophilic macrocycles were active in the two in vitro tests but not against chicken coccidiosis. One compound was tested in cattle and was found to increase levels of propionic acid in the rumen fermentation. This effect is considered an important factor for increasing the efficiency of feed utilization in cattle exhibited by the ionophore antibiotic monensin. The alkali ion salts of these lipophilic macrocyclic polyether carboxylic acids are very soluble in organic solvents and insoluble in water. These compounds are proposed to act as ion-transport agents and functional mimics of the ionophore antibiotics in the biological systems described above.
Urban
F J
FJ
Pfizer Central Research, Groton, Connecticut 06340.
Chappel
L R
LR
Girard
A E
AE
Mylari
B L
BL
Pimblett
I J
IJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D002627:Chemistry, Physical; D015195:Drug Design; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D007476:Ionophores / Q000138:chemical synthesis* / Q000494:pharmacology; D011422:Propionates / Q000378:metabolism; D012417:Rumen / Q000187:drug effects
D000900:Anti-Bacterial Agents; D004988:Ethers, Cyclic; D007476:Ionophores; D011422:Propionates; C029658:propionic acid